The effects of benzodiazepine agonists, inverse agonists and Ro 15-1788 on the responses of the superior cervical ganglion to GABA in vitro.

Abstract

The effects of benzodiazepines and their antagonists on the responses to gamma-aminobutyric acid (GABA) of the superior cervical ganglion of the rat were examined using extracellular recording. Chlordiazepoxide (1 microM to 28.9 microM) and flurazepam (145-725 nM) increased the responses of the ganglion to GABA and the increases were antagonized by Ro 15-1788, at 3.34 microM. The concentration of GABA used was 9.7 microM which gave half-maximal responses. Chlordiazepoxide similarly increased the responses of the ganglion to GABA 38.8 microM in the presence of bicuculline 27.2 microM. This concentration of GABA gave, with bicuculline, responses of a similar magnitude as those to 9.7 microM in the absence of bicuculline. Bicuculline did not affect the actions of chlordiazepoxide or the antagonism by Ro 15-1788. Ro 15-1788 did not affect the increases in GABA response caused by pentobarbitone or by phenobarbitone in the presence of bicuculline. Ethyl beta-carboline-3-carboxylate (beta CCE) (207 nM to 1 microM) significantly decreased the responses to GABA in the presence and in the absence of bicuculline. The decreases were antagonized by Ro 15-1788 (3.34 microM). beta CCE at 2.1 microM and above did not significantly change the responses to GABA. Methyl beta-carboline-3-carboxylate (beta CCM) at 88 to 440 nM significantly decreased the responses to GABA. The decreases were antagonized by Ro 15-1788 (3.34 microM) and were also seen in the presence of bicuculline. High concentrations of Ro 15-1788 decreased the responses to GABA, 9.7 microM, but increased the responses to GABA 38.8 microM in the presence of 27.2 microM bicuculline. The pattern of effects of the benzodiazepines, beta-carbolines and low doses of Ro 15-1788 on the responses to GABA was similar to the effects of these compounds on seizure threshold and anxiety-related behaviour in vivo.